Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. The hallmark of the disease is retinal pigment epithelial (RPE) dysfunction with subsequent death of the foveal photoreceptors. Hematopoietic stem cells (HSC) have been demonstrated to repair damaged tissues including heart muscle and nerve under selected conditions. Allogeneic RPE transplantation has been attempted to restore the damaged RPE. However, allogeneic RPE cells do not attach to senescent Bruch's membrane efficiently, and do not efficiently repair the defect. Furthermore, rejection occurs after allogeneic adult RPE transplantation unless immunosuppression is employed. Thus, the development of a syngeneic HSC product (AMD-FCRx) to treat AMD and avoid the need for systemic immunosuppression would be a major advance. We were the first to discover CD8+/TCR- graft facilitating cells (FC), a novel cell in bone marrow that significantly enhances HSC engraftment in syngeneic recipients. FC express SDF-1, a critical chemokine for HSC homing, and CXCR4, its unique receptor that is also present on HSC We have strong preliminary data to show that FC enhance homing of HSC to damaged RPE. As such, FC may play a critical role in HSC-mediated repair of damaged RPE. In phase I of this application we will define the optimal composition of HSC and FC for transplantation to replace damaged RPE. Specifically, we will optimize strategies to promote homing of HSC to areas of RPE damage or loss, attach to normal Bruch's membrane, proliferate and fill in the defect created, and differentiate into mature RPE cells. These studies will lay the groundwork for Phase II in which the AMD-FCRx product will be tested in a more rigorous model of AMD and then translated into a phase I clinical protocol. Regenerex, LLC has been incorporated to commercialize the benefits of bone marrow graft engineering technologies for treatment of blood disorders and tissue repair. We have assembled a highly talented team with expertise in ophthalmology, stem cell biology, and transplantation. A unique collaboration between the Louisville Medical Center Development Corporation, Jewish Hospital, the State of Kentucky, and the University of Louisville to develop a biomedical incubator has allowed Regenerex, LLC to move into office space located at 201 East Jefferson Street. Our long-term goal is to exploit the potential of the facilitating cell by marketing a well-defined HSC cellular therapeutic product for worldwide distribution to treat AMD. Regenerex is a woman-owned business in Kentucky, an EPSCoR state.